Epigenetic imprinting alterations as effective diagnostic biomarkers for early-stage lung cancer and small pulmonary nodules
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Published:2021-12
Issue:1
Volume:13
Page:
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ISSN:1868-7075
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Container-title:Clinical Epigenetics
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language:en
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Short-container-title:Clin Epigenet
Author:
Zhou Jian, Cheng Tong, Li Xing, Hu Jie, Li Encheng, Ding Ming, Shen Rulong, Pineda John P., Li Chun, Lu Shaohua, Yu Hongyu, Sun Jiayuan, Huang Wenbin, Wang Xiaonan, Si Han, Shi Panying, Liu Jing, Chang Meijia, Dou Maosen, Shi Meng, Chen Xiaofeng, Yung Rex C., Wang Qi, Zhou Ning, Bai ChunxueORCID
Abstract
Abstract
Background
Early lung cancer detection remains a clinical challenge for standard diagnostic biopsies due to insufficient tumor morphological evidence. As epigenetic alterations precede morphological changes, expression alterations of certain imprinted genes could serve as actionable diagnostic biomarkers for malignant lung lesions.
Results
Using the previously established quantitative chromogenic imprinted gene in situ hybridization (QCIGISH) method, elevated aberrant allelic expression of imprinted genes GNAS, GRB10, SNRPN and HM13 was observed in lung cancers over benign lesions and normal controls, which were pathologically confirmed among histologically stained normal, paracancerous and malignant tissue sections. Based on the differential imprinting signatures, a diagnostic grading model was built on 246 formalin-fixed and paraffin-embedded (FFPE) surgically resected lung tissue specimens, tested against 30 lung cytology and small biopsy specimens, and blindly validated in an independent cohort of 155 patients. The QCIGISH diagnostic model demonstrated 99.1% sensitivity (95% CI 97.5–100.0%) and 92.1% specificity (95% CI 83.5–100.0%) in the blinded validation set. Of particular importance, QCIGISH achieved 97.1% sensitivity (95% CI 91.6–100.0%) for carcinoma in situ to stage IB cancers with 100% sensitivity and 91.7% specificity (95% CI 76.0–100.0%) noted for pulmonary nodules with diameters ≤ 2 cm.
Conclusions
Our findings demonstrated the diagnostic value of epigenetic imprinting alterations as highly accurate translational biomarkers for a more definitive diagnosis of suspicious lung lesions.
Funder
zhongshan hospital clinical research foundation national natural science foundation of china national major scientific and technological special project shanghai municipal key clinical specialty science and technology commission of shanghai municipality jiangsu science and technology development project
Publisher
Springer Science and Business Media LLC
Subject
Genetics (clinical),Developmental Biology,Genetics,Molecular Biology
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